Perinatal carcinogenesis is determined and modulated in part by maternal and fetal metabolic activation and detoxification of the initiating chemical and by postnatal influences on tumor development. The influence of metabolism has been definitively demonstrated and investigated in depth for a polycyclic aromatic hydrocarbon (PAH), 3-methylcholanthrene. Recent highlights include implication of hydroxylation at the 3-methyl position as a critical step in activation. This work is being extended to other PAHs of environmental importance, including 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene (BP), and to investigation of BP activation in fetuses of patas monkeys, as indicated by both enzyme assay and Western immunoblot, and 32P-postlabeling (with Dr. L.J. Lu) (see Project Z01CP05092). Patas fetal and placental BP metabolism, both basal and inducible, share important features with the human. Study of the role of maternal/fetal carcinogen metabolism is now being extended in both the mouse and the monkey to include the arylamine food mutagens, starting with 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). With regard to postnatal effects, attention has focussed on the polychlorinated hydrocarbons (PCHS) that are effectively delivered in the milk of humans and animals. To mimic this effect, tumors were initiated in newborn mice by N-nitrosodimethylamine (NDMA), followed by i.g. PCH mixtures or single con- geners. A tumor promotive effect of the latter treatment in liver and lung was confirmed, and results with individual congeners suggested involvement of the Ah locus (controlling cytochrome P450 IA induction) in the lung tumor promotion. These Ah-agonist congeners were found to be selectively retained in lung, and Ah-dependent enzyme induction was persistent for at least 12 weeks after a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin and for at least 30 weeks after a dose of a PCH mixture. Study of the role of these phenomena in postnatal promotion is ongoing, including use of tobacco-specific nitrosamines as perinatal initiators.